Clinical Trial: Lenalidomide in Combination With Melphalan and Dexamethasone in Newly-diagnosed Light-chain (AL)-Amyloidosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multicenter Phase I/II Dose Escalation Study of Lenalidomide in Combination With Melphalan and Dexamethasone in Subjects With Newly-diagnosed Light-chain (AL)-Amyloidosis

Brief Summary: Amyloidosis results from tissue deposition of amyloid protein, composed mainly by the fragments of monoclonal immunoglobulin heavy chains or light chains. Accumulation of amyloid protein progressively disrupts normal tissue structure and ultimately leads to organ failure, most frequently in the kidneys, heart, liver and peripheral nervous system. A recently completed French prospective randomized trial, in patients presenting with newly AL-amyloidosis, compared two treatment regimens at the time of diagnosis: Melphalan-dexamethasone (conventional oral treatment), versus high dose of Melphalan followed by autologous stem cell transplantation (ASCT) (1). High-dose therapy was not associated with a better outcome. Melphalan-dex given monthly can be considered as the current standard of care, with a median survival of 56 months. The use of a combination of lenalidomide and dexamethasone has already been tested in patients with AL-amyloidosis (2). The initial dose of lenalidomide at 25 mg/day was poorly tolerated. However, a 15 mg/day dose regimen was well tolerated and effective, with an overall hematologic response rate of 67%. Hematologic responses were associated with clinical responses. Dispenzieri et al confirmed that the combination of Lenalidomide + dexamethasone achieved a 75% hematologic response rate, with a 42% organ response, and a median follow-up of 17 months in patients still receiving treatment (2006). These authors also recommended a lower dose of 15mg/day. The rationale for the present investigation is that addition of lenalidomide to the current standard of care (Melphalan-dexamethasone) might improve the hematologic response rate and the organ response rates both associated with a prolonged survival in patients with AL-amyloidosis. As the toxicity of the combination of M-dex + lenalidomide is unknown in patients with AL-amyloidosis, the dose of lenalidomide will start from the lowest one available, i.e., 5 mg/day and increased from 5 to 5 mg up to a

Detailed Summary:
Sponsor: Nantes University Hospital

Current Primary Outcome: Determination of MTD by evaluation of hematological and non hematological toxicity

Original Primary Outcome: The primary endpoint is to evaluate the incidence of dose limiting toxicities (DLT) during the first cycle of lenalidomide at a given dose level in order to determine the maximal tolerated dose (MTD) in a dose escalating study design.

Current Secondary Outcome:

• Complete (CR) or partial (PR) response, according to criteria defined during the 10th International Symposium on Amyloidosis
  To determine the hematologic response
• disease progression from the date of the first dose to the date of the first observation of organ disease progression and observation of response
  To determine the rate of organ response
• Value of frequent measurements of free light chain assays
  To determine interest of frequent measurments of free light chain assays for patients
• Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and laboratory abnormalities
  To assess the safety profile of the combination therapy
• time between first documentation of hematologic response and disease progression
  To measure hematological duration
• disease progression from the date of the first dose to the date of the first observation of hematologic disease progression
  Time to hematologic disease progression

Original Secondary Outcome: To determine the hematologic response, the rate of organ response, explore the value of frequent measurements of free light chain assays, assess the safety profile of the combination therapy

Information By: Nantes University Hospital

Dates:
Date Received: February 12, 2008
Date Started: January 2008
Date Completion:
Last Updated: May 9, 2011
Last Verified: May 2010